title: TREM2 in neurodegeneration: evidence for association of the p.R47H variant with frontotemporal dementia and Parkinson's disease.
abstract: BACKGROUND
  A rare variant in the Triggering Receptor Expressed on Myeloid cells 2 (TREM2) gene has been reported to be a genetic risk factor for Alzheimer's disease by two independent groups (Odds ratio between 2.9-4.5). Given the key role of TREM2 in the effective phagocytosis of apoptotic neuronal cells by microglia, we hypothesized that dysfunction of TREM2 may play a more generalized role in neurodegeneration. With this in mind we set out to assess the genetic association of the Alzheimer's disease-related risk variant in TREM2 (rs75932628, p.R47H) with other related neurodegenerative disorders.
  
  
  RESULTS
  The study included 609 patients with frontotemporal dementia, 765 with amyotrophic lateral sclerosis, 1493 with Parkinson's disease, 772 with progressive supranuclear palsy, 448 with ischemic stroke and 1957 controls subjects free of neurodegenerative disease. A significant association was observed for the TREM2 p.R47H substitution in susceptibility to frontotemporal dementia (OR = 5.06; p-value = 0.001) and Parkinson's disease (OR = 2.67; p-value = 0.026), while no evidence of association with risk of amyotrophic lateral sclerosis, progressive supranuclear palsy or ischemic stroke was observed.
  
  
  CONCLUSIONS
  Our results suggest that the TREM2 p.R47H substitution is a risk factor for frontotemporal dementia and Parkinson's disease in addition to Alzheimer's disease. These findings suggest a more general role for TREM2 dysfunction in neurodegeneration, which could be related to its role in the immune response.
authors.affiliation: Department of Neuroscience, Mayo Clinic, Jacksonville, FL, USA.
authors.forename: Sruti
authors.initials: S
authors.lastname: Rayaprolu
authors.forename: Bianca
authors.initials: B
authors.lastname: Mullen
authors.forename: Matt
authors.initials: M
authors.lastname: Baker
authors.forename: Timothy
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authors.lastname: Lynch
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authors.lastname: Finger
authors.forename: William W
authors.initials: WW
authors.lastname: Seeley
authors.forename: Kimmo J
authors.initials: KJ
authors.lastname: Hatanpaa
authors.forename: Catherine
authors.initials: C
authors.lastname: Lomen-Hoerth
authors.forename: Andrew
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authors.lastname: Kertesz
authors.forename: Eileen H
authors.initials: EH
authors.lastname: Bigio
authors.forename: Carol
authors.initials: C
authors.lastname: Lippa
authors.forename: Keith A
authors.initials: KA
authors.lastname: Josephs
authors.forename: David S
authors.initials: DS
authors.lastname: Knopman
authors.forename: Charles L
authors.initials: CL
authors.lastname: White
authors.forename: Richard
authors.initials: R
authors.lastname: Caselli
authors.forename: Ian R
authors.initials: IR
authors.lastname: Mackenzie
authors.forename: Bruce L
authors.initials: BL
authors.lastname: Miller
authors.forename: Magdalena
authors.initials: M
authors.lastname: Boczarska-Jedynak
authors.forename: Grzegorz
authors.initials: G
authors.lastname: Opala
authors.forename: Anna
authors.initials: A
authors.lastname: Krygowska-Wajs
authors.forename: Maria
authors.initials: M
authors.lastname: Barcikowska
authors.forename: Steven G
authors.initials: SG
authors.lastname: Younkin
authors.forename: Ronald C
authors.initials: RC
authors.lastname: Petersen
authors.forename: Nilüfer
authors.initials: N
authors.lastname: Ertekin-Taner
authors.forename: Ryan J
authors.initials: RJ
authors.lastname: Uitti
authors.forename: James F
authors.initials: JF
authors.lastname: Meschia
authors.forename: Kevin B
authors.initials: KB
authors.lastname: Boylan
authors.forename: Bradley F
authors.initials: BF
authors.lastname: Boeve
authors.forename: Neill R
authors.initials: NR
authors.lastname: Graff-Radford
authors.forename: Zbigniew K
authors.initials: ZK
authors.lastname: Wszolek
authors.forename: Dennis W
authors.initials: DW
authors.lastname: Dickson
authors.forename: Rosa
authors.initials: R
authors.lastname: Rademakers
authors.forename: Owen A
authors.initials: OA
authors.lastname: Ross
mesh_terms: D000368:Aged; D005260:Female; D057180:Frontotemporal Dementia / Q000235:genetics*; D005787:Gene Frequency; D020022:Genetic Predisposition to Disease / Q000235:genetics*; D005838:Genotype; D006801:Humans; D008297:Male; D008562:Membrane Glycoproteins / Q000235:genetics*; D008875:Middle Aged; D019636:Neurodegenerative Diseases / Q000235:genetics; D010300:Parkinson Disease / Q000235:genetics*; D020641:Polymorphism, Single Nucleotide; D060888:Real-Time Polymerase Chain Reaction; D011971:Receptors, Immunologic / Q000235:genetics*
chemical_list: D008562:Membrane Glycoproteins; D011971:Receptors, Immunologic; C498715:TREM2 protein, human